The objective of this proposal is to characterize the immunobiology of an orthotopically transplanted murine colonic tumor. Implantation of a syngeneic murine colon adenocarcinoma into the submucosa of the bowel wall results in a primary tumor that eventually metastasizes both to the mesenteric lymph node and to the liver. Thus, this model simulates the natural history of human colon disease. Lymphoid tissue is extensively distributed throughout the submucosa of the bowel and is part of a local immune system that may be a focus of host resistance as well as a mediator of enhancement of growth of a malignant neoplasm. Temporal studies of specific antitumor immunity will be performed with lymphoid tissues of the local (Peyer's patches) immune system, and this will be compared to lymphoid tissues obtained from the regional (mesenteric nodes) and systemic (peritoneal cells, spleen) immune system. Furthermore, the role of blocking factors and suppressor cells in preventing these effector mechanism, promoting continued growth, and metastasis of the primary tumor will also be evaluated. This project will provide information on the nature of effector mechanisms associated with the local immune response, evaluate the role of the local immune response in promoting metastases, and open up new avenues of research for both immunodiagnosis and immunotherapy of human colon cancer.